Nearly 46 million Americans have erectile dysfunction (ED), and approximately 35% to 50% of all men aged 40 to 70 have some form of ED. Present therapies for ED are often rejected by patients within 1 to 3 years due to loss of efficacy, side effects, or permanent damage to erectile tissue. Erection has been generated by electrical stimulation of a peripheral nerve in animals and is not expected to lose efficacy or cause the side effects or irreversible damage associated with present therapies. The long-term goal of this project is to develop and commercialize a neurostimulation product that would electrically stimulate the peripheral nerve to generate erection in men with vasculogenic erectile dysfunction. The project will determine the feasibility of using an electrode lead placed in the pelvis near the peripheral nerve to achieve a sustained erection in the acute animal model. The first two specific aims of this Phase I project are to determine the feasibility of using electrical stimulation of the peripheral nerve to 1) evoke and 2) sustain a penile erection that is comparable to intracavernous injection of alprostadil (the gold standard for clinical treatment efficacy) in cats. The hypotheses are that electrical stimulation of the peripheral nerve will 1) elicit and 2) sustain a penile erection that is sustained for the duration of stimulation up to 30 minutes, and the corpus cavernous pressure (CCP) evoked by peripheral nerve stimulation will be greater than or equal to the CCP evoked by alprostadil. The third specific aim is to 3) validate in the animal model a technique that can later be used to translate these results to humans if specific aims # 1 and # 2 are successful. The hypothesis is that 3) in the animal model, percutaneous electrical stimulation will elicit and sustain an erection through a minimally invasive two- contact electrode placed in the pelvis, and the CCP evoked by percutaneous stimulation will be greater than or equal to the CCP evoked by alprostadil. At the conclusion of this project, we will have determined the feasibility of evoking and sustaining an erection via electrical stimulation of the peripheral nerve that is comparable to the clinical gold standard in the animal model. If it is determined to be feasible, this approach will be developed into a minimally invasive neural prosthesis that does not cause the side effects or damage caused by present ED therapies. Over 70% of the 46 million Americans with erectile dysfunction (ED) report that their quality of life is moderately to severely reduced by ED, and over 70% of men with ED feel hurt by the response of their partner to their ED and feel ? to some extent a failure? because of their ED. Thus, ED is often associated with poor self- image, depression, and it can affect interpersonal relationships and lead to increased mental stress. We propose to develop a minimally invasive treatment for ED that does not cause the side effects or damage caused by current ED therapies. [unreadable] [unreadable] [unreadable]